Synthesis of adamantane-based trimeric cationic surfactants

Article abstract of DOI:10.1080/00397911.2011.625134

Three trimeric quaternary ammonium surfactants, having adamantane cores and different carbon chains, were synthesized using adamantane as the starting raw material. The target compounds were confirmed by elemental analysis, ¹H NMR, ¹³C NMR, and mass spectroscopy. The influences of reaction conditions on the yields of the key intermediate product 1,3,5-trihydroxyadamantane (3) were investigated. Surface properties of the target compounds were measured. The critical micelle concentration values of 1a, 1b, and 1c were 2mM, 1mM, and 0.5mM, respectively.

Full text of DOI:10.1080/00397911.2011.625134

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Synthesis of Adamantane-Based Trimeric
Cationic Surfactants
a
a
a
b
a
Hua Zhu , Jianwei Guo , Chufen Yang , Sa Liu , Yingde Cui
&
a
Xing Zhong
a
Faculty of Chemical Engineering and Light Industry, Guangdong
University of Technology, Guangzhou, China
b
Biomedical Engineering Institute, South China University of
Technology, Guangzhou, China
Accepted author version posted online: 22 Feb 2012.Version of
record first published: 21 Feb 2013.
To cite this article: Hua Zhu , Jianwei Guo , Chufen Yang , Sa Liu , Yingde Cui & Xing Zhong (2013):
Synthesis of Adamantane-Based Trimeric Cationic Surfactants, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 43:8, 1161-1167
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1
Synthetic Communications , 43: 1161–1167, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.625134
SYNTHESIS OF ADAMANTANE-BASED TRIMERIC
CATIONIC SURFACTANTS
1
Hua Zhu, Jianwei Guo, Chufen Yang, Sa Liu, Yingde Cui,
1
1
2
1
1
and Xing Zhong
1
Faculty of Chemical Engineering and Light Industry, Guangdong
University of Technology, Guangzhou, China
2
Biomedical Engineering Institute, South China University of Technology,
Guangzhou, China
GRAPHICAL ABSTRACT
Abstract Three trimeric quaternary ammonium surfactants, having adamantane cores and
different carbon chains, were synthesized using adamantane as the starting raw material.
1
13
The target compounds were confirmed by elemental analysis, H NMR, C NMR, and mass
spectroscopy. The influences of reaction conditions on the yields of the key intermediate
product 1,3,5-trihydroxyadamantane (3) were investigated. Surface properties of the target
compounds were measured. The critical micelle concentration values of 1a, 1b, and 1c were
2
mM, 1 mM, and 0.5 mM, respectively.
Keywords Adamantane; critical micelle concentration; trimeric cationic surfactant
INTRODUCTION
In recent years, the unusual qualities such as high surface activity, low critical
micelle concentration (CMC), and diverse aggregate structures of Gemini surfactants,
which contain double hydrophobic chains and hydrophilic headgroups linked by
[
1–5]
spacer groups, have been realized.
of higher oligomeric analogs.
This has raised questions about the behavior
However, only a limited number of trimeric
surfactants have been synthesized and studied so far, even though the properties of
[
6,7]
Received April 25, 2011.
Address correspondence to Jianwei Guo, Faculty of Chemical Engineering and Light Industry,
Guangdong University of Technology, 100 Waihuan Xi Road, HEMC Panyu District, Guangzhou
510006, China. E-mail: doctorgjw@163.com
1
161

1162
H. ZHU ET AL.
oligomeric surfactants have been found to be better than corresponding dimeric
[
8–10]
homologs. Recently a few kinds of trimeric quaternary ammonium halide sur-
factants with different spacer groups were synthesized and investigated.
[
11–15]
It
was found that the spacer groups exerted important influence on the behavior of
oligomeric surfactants.
Adamantane is a highly symmetric cage-like hydrocarbon with the molecular
formula C H , where the six methylene groups form an octahedron and the four
1
0
16
[
16,17]
methane groups projecting out form a tetrahedron.
The special structure of ada-
mantane gives it many useful chemical and physical properties, such as high boiling
point, good thermal stability, and nontoxicity. The bridge carbon atoms of adaman-
tane are active, which allows substitution, oxidation, and alkylation reactions to take
[
18]
place, producing a wide variety of adamantane derivatives. This make adamantane
devisable and able to be used as the spacer of oligomeric surfactants, which may have
low CMC value, high antibacterial properties, and foam performance.
In this article, adamantane was used as the spacer group to synthesize a trimeric
quaternary ammonium halide surfactant. To make the target trimeric cationic surfac-
tant degradable, bromoacetyl bromide was introduced into the adamantane structure
to produce ester groups after the hydroxylation reaction of adamantane. Sub-
sequently the alkyl (alkyl ¼ C , C , C ) tertiary amines in which the alkyl groups
8
10
12
acted as hydrophobic building blocks were connected to the spacers by a quateriza-
tion reaction to give the corresponding quaternary amine trimeric surfactants.
Additionally, the CMC of the synthesized trimeric cationic surfactants was measured.
The antibacterial property and foam performance will be reported elsewhere.
RESULTS AND DISCUSSION
Synthesis
To make the target compounds easy to degrade, the trimeric cationic surfac-
tants were designed to contain ester groups, and thus the target compounds were
synthesized in the following steps: First, the adamantane spacer was oxidized by
chromium trioxide to produce 1,3,5-trihydroxyadamantane 3. Then the 1,3,5-
trihydroxyadamantane 3 was esterized by bromoacetyl bromide to give 1,3,5-trikis
(
bromoacetoxy)adamantane 2. Subsequently three alkyl (alkyl ¼ C , C , C ) tertiary
8
10
12
amines were connected to the spacers by quaterization to give the corresponding
quaternary amine cationic surfactants 1 (shown in Scheme 1).
Influences of Reaction Conditions
The last two steps were classical reactions and had excellent yield without opti-
mization in this study, whereas on the first step reaction, the oxidation conditions of
adamantane including molar ratio of CrO =adamantane (ADH), temperature, and
3
reaction time were investigated. For the oxidation reaction of adamantane, several
oxidizing agents have been reported, including hypochlorous acid and methyl
[19,20]
(trifluoromethyl)dioxirane.
However, both of them had some shortcomings.
The selectivity and yield of the reaction using hypochlorous acid as oxidizing agent
were quite poor, and difficult to separate, and the other oxidizing agent is expensive

SYNTHESIS OF TRIMERIC SURFACTANTS
1163
Scheme 1. Synthesis of 1.
and unstable. Therefore, in this article, another oxidizing agent, CrO , was employed
3
to obtain the intermediate 1,3,5-trihydroxyadamantane (3), which had been used by
[
21]
Landa et al. in 1967
hydroxy products. The results are shown in Table 1.
to oxidize adamantane to form its corresponding single-
The molar ratio of CrO and ADH had a deep effect on the yield of 1,3,5-
3
trihydroxyadamantane. The maximum yield reached 50.1% when the molar ratio
was 10, but the yield of 3 decreased as the molar ratio increased. This was because
in this oxidation reaction, four products (1-hydroxyadamantane, 1,3-dihydroxyada-
mantane, 1,3,5-trihydroxyadamantane, and 1,3,5,7-tetrahydroxy-adamantane) can
be obtained under different conditions. When the molar ratio of CrO and ADH
3
was 10, the main product was 1,3,5-trihydroxyadamantane 3, whereas with less
oxidation reagent, most of adamantane was oxidated to 1-hydroxy-adamantane
and 1,3-dihydroxyadamantane, and with more oxidation reagent, the main product
was 1,3,5,7-tetrahydrogxyadamantane.
As most of organic reactions have to be heated, commonly the reaction ratio at
low temperature was slow and had poor yield. In this study, it was found that when
the oxidation reagent was added to the reaction, temperature would increase and the
ꢀ
reaction could happen at 80 C. However, this temperature was not the optimal
Table 1. Effects of reaction conditions on yield of 3
ꢀ
No. CrO
3
=ADH (mol ratio) Temperature ( C) Time (h) Yield (%)
1
2
3
4
5
6
7
8
9
5
5
100
110
90
3
2
1
1
1
2
3
1
1
4.2
3.1
33
50
45
50
49
30
11
10
10
10
10
10
15
20
100
110
100
100
100
100
Note. Acetic acid as solvent.

1164
H. ZHU ET AL.
Figure 1. Surface tension of 1 water solutions. (Figure is provided in color online.)
temperature. The subsequent investigation showed that reaction yield was much
ꢀ
ꢀ
greater when the reaction temperature was 100 C, and the yield at 110 C was less.
It may have been caused by the sublimation of adamantane, because more adaman-
ꢀ
tane escaped from the reaction system when temperature above 100 C, or it might
ꢀ
be induced by the ring-opening reaction, which happens more easily at 110 C.
Furthermore, when the reaction time was more than 1 h, the yield of 3 slowly
decreased with prolonged reaction time. The reason for this consequence may be that
more adamantane was oxidized to the by-product, 1,3,5,7-tetrahydroxyadamantane.
Surface-Active Properties
CMC is the most common descriptor of surfactant systems. The CMC value is
usually detected by plotting surface tension vs log concentration. The surface tension
will decrease as the concentration of the solution increases, until it reaches CMC,
when a sharp bend appears in the plot. Figure 1 shows the results of the synthesized
trimeric surfactant concentrations and their corresponding surface tensions. In Fig. 1
the break points correspond to the CMC of 2 mM, 1 mM, and 0.5 mM, which repre-
sents the CMC of the synthesized trimeric surfactants 1a, 1b, and 1c respectively.
These values lay far below the CMC of monomeric surfactants (C TAB, 290 Mm;
8
[
22]
C TAB, 65 mM; and C TAB, 14.6 mM).
1
0
12
CONCLUSIONS
The trimeric cationic surfactants, 1,3,5-trikis(dimethyl-alkyl-ammonio-acetoxy)
adamantane tribromide (alkyl ¼ C , C , C ), were successfully synthesized using
8
10
12
adamantane as raw material by oxidation, esterification, and quaterization reactions

SYNTHESIS OF TRIMERIC SURFACTANTS
1165
successively. Synthesis of 1,3,5-trihydroxyadamantane (3) was a crucial reaction. The
influences of reaction conditions on the yields of 3 were investigated. It was found that
the greatest yield (50.1%) of 1,3,5-trihydroxyadamantane (3) could be obtained under
ꢀ
the conditions of 100 C, 1 h, and CrO =ADH ¼ 10. The CMC of the trimeric cationic
3
surfactants 1a, 1b, and 1c were 2 mM, 1 mM, and 0.5 mM respectively, which were far
less than the values of their corresponding monomeric surfactants.
EXPERIMENTAL
Melting points are uncorrected. All reactions were carried out under a nitrogen
atmosphere. Solvents were reagent grade and in most cases dried prior to use. All
reagents were purchased from Aladdin. Amines were redistilled prior to use. Column
1
chromatography was performed on silica gel 60 (Merk 230 400 mesh). H NMR and
3
1
C NMR spectra were recorded on a Varian Mercury-plus 300 spectrometer at
00 MHz and 75 MHz respectively. Mass spectra were recorded on a LCMS-2020
3
instrument. Tensiometry was performed using freshly prepared solutions with
a KSV Sigma 700 tensiometer by the ring method: Each point was tested five times,
and the average was used.
Synthesis of 1,3,5-Trihydroxyadamantane 3
A mixture of adamantane (13.6 g, 0.1 mol) and acetic acid (100 g, 1.67 mol) were
ꢀ
added to a 200-mL, three-neck flask and stirred at 80 C. Chromic acid solution,
which was prepared by dissolving quantitative chromium trioxide (100 g, 1.0 mol)
into 54 mL of water, was added dropwise into the former mixture, and the reaction
ꢀ
ꢀ
temperature was kept below 100 C. Then, the mixture was heated to 100 C and kept
there for 1h. The solvent was removed by vacuum distillation, and sodium hydroxide,
solution was added to the residue for neutralization and extracted by boiling ethyl
acetate (5 ꢁ 200 mL). The extract was left standing overnight; the white precipitate
ꢀ
1
was obtained by filtration. Yield 8.5 g (50.1%), mp 203–205 C. H NMR (DMSO-d ,
6
300 MHz) d: 4.50 (s, 3H), 2.10 (s, 1H), 1.33–1.42 (m, 12H). Anal. calcd for C H O :
10 16 3
C, 65.19; H, 8.75. Found: C, 65.14; H, 8.74.
Synthesis of 1,3,5-Trikis(bromoacetoxy)adamantane 2
A catalytic amount (20 mg) of 4-(dimethylamino)pyridine (DMAP) was added
to a stirred suspension of 1,3,5-trihydroxyadamantane (1.47 g, 7.99 mmol) in 2.0 mL
of pyridine (24.6 mmol) and 12 mL of CH CN. BrCH COBr (4.12 mL, 47.2 mmol)
3
2
ꢀ
was then added dropwise at 0 C over 1 h. The mixture was stirred and kept at
ꢀ
60 C for 5 h. After that, the solution became transparent and homogeneous. Six
mL of HCl (6 M) was added to the reaction mixture together with 10 mL of CH Cl .
2
2
The aqueous layer was extracted with CH Cl (3 ꢁ 12 mL), and the combined organic
2
2
layers were concentrated to give a light-brown liquid residue. The liquid was dissolved
in 10 mL of CH Cl and washed with brine and 10 mL of aqueous 0.5 M Na CO .
2
2
2
3
After that the organic layer turned brown-black. This was concentrated and purified
by filtering through a silica-gel column. Elution with CH Cl gave the desired product
2
2
1
as a yellow-white liquid, yielding 3.56 g (82%). H NMR (CDCl ) d: 3.76 (s, 6H), 2.56
3

1166
H. ZHU ET AL.
1
3
(
m, 7H), 2.10 (d, 6H); C NMR (DMSO-d ) d: 168.7, 84.0, 82.4, 62.9, 46.241, 31.3.
6
Anal. calcd. for C H Br O : C, 35.13; H, 3.50; Br, 43.82. Found: C, 35.29; H, 3.45;
Br, 43.46.
1
6
19
3
6
General Procedure for the Preparation of the Trimeric Surfactants
In a round-bottom flask, 1.11 g (2.03 mmol) of 1,3,5-trikis(bromoacetoxy)-
adamantane was dissolved in 20 mL of acetone, and was added tertiary amine
(
9.14 mmol) to the clear solution in one portion. The solution was vigorously stirred
ꢀ
for 3 h at 30 C, during which a white precipitate formed gradually. The precipitate
was filtered and then washed several times with acetone to give a white solid.
1
,3,5-Trikis(dimethyloctylammonioacetoxy)adamantane
tribromide
ꢀ
1
a. Recrystallized from CH CN=acetone: yield 86%; mp 196.1–196.9 C; H NMR
1
3
(
(
1
2
5
CD CN) d 4.31 (s, 6H), 3.46 (m, 6H), 3.19 (s, 18H), 2.52 (s, 7H), 2.04(s, 6H), 1.65
3
1
3
m, 6H), 1.33–1.23 (m, 30H), 0.84 (t, 9H, J ¼ 6.6 Hz); C NMR (DMSO-d ) d:
6
64.3, 82.9, 65.5, 61.7, 51.8, 43.9, 32.1, 29.3, 29.3, 26.5, 22.9, 22.7, 14.6; ESI-MS:
3
59 (68%) (M-3Br) , 429 (100%) (M-2Br) . Anal. calcd. for C H Br N O : C,
þ
2þ
4
6
88
3
3
6
4.22; H, 8.71; N, 4.12; Br, 23.53. Found: C, 54.12; H, 8.73; N, 4.29; Br, 23.46.
1
,3,5-Trikis(dimethyldecylammonioacetoxy)adamantane tribromide
ꢀ
b. Recrystallized from CH CN=acetone: yield 83%; mp 194.8–196.3 C; H NMR
3
1
1
(
(
8
2
5
CD CN) d 4.29 (s, 6H), 3.48 (m, 6H), 3.23 (s, 18H), 2.59 (s, 7H), 2.10 (s, 6H), 1.70
3
13
m, 6H), 1.31–1.21 (m, 42H), 0.87 (t, 9H, J ¼ 6.6 Hz); C NMR (DMSO-d ) d: 164.3,
6
2.9, 65.5, 61.7, 51.8, 43.9, 32.1, 29.7, 29.6, 29.5, 29.3, 26.5, 22.9, 22.7, 14.8; ESI-MS:
3þ
2þ
88 (100%) (M-3Br) , 472 (70%) (M-2Br) . Anal. calcd for C H Br N O : C,
5
2
100
3
3 6
6.62; H, 9.14; N, 3.81; Br, 21.73. Found: C, 56.49; H, 9.23; N, 3.93; Br, 21.65.
1
,3,5-Trikis(dimethyldodecylammonioacetoxy)adamantane tribromide
ꢀ
c. Recrystallized from CH CN=acetone: yield 80%; mp 193.9–195.7 C; H NMR
3
1
1
(
(
1
2
CD CN) d 4.25 (s, 6H), 3.45 (m, 6H), 3.19 (s, 18H), 2.56 (s, 7H), 2.08 (s, 6H), 1.68
3
1
3
m, 6H), 1.33–1.23 (m, 54H), 0.87 (t, 9H, J ¼ 6.8 Hz); C NMR (DMSO-d ) d:
6
64.3, 82.9, 65.5, 61.7, 51.8, 43.9, 32.1, 29.9, 29.8, 29.6, 29.6, 29.3, 29.3, 26.5, 22.9,
3
2.7, 14.8; ESI-MS: 316 (100%) (M-3Br) , 514 (57%) (M-2Br) . Anal. calcd. for
þ
2þ
C H Br N O : C, 58.68; H, 9.51; N, 3.54; Br, 20.19. Found: C, 58.59; H, 9.63;
6
5
8
112
3
3
N, 3.69; Br, 20.20.
ACKNOWLEDGMENT
This work was financially supported by the Major Program of Guangdong
University of Technology (No. 405095220).
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